<i>Escherichia coli</i>Braun Lipoprotein Induces a Lipopolysaccharide-Like Endotoxic Response from Primary Human Endothelial Cells

Neilsen, Paul O.; Zimmerman, Guy A.; McIntyre, Thomas M.

doi:10.4049/jimmunol.167.9.5231

Cited by 42 publications

(41 citation statements)

References 59 publications

(36 reference statements)

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“…LPS, but Not an Endotoxic Lipopeptide, Desensitized Endothelial Cells to Commercial Ovalbumin-We explored the nature of the inflammatory agent in commercial ovalbumin by distinguishing LPS from non-LPS endotoxins, because both prokaryotic proteins displaying a lipid-modified N-terminal cysteinyl residue and LPS are a potent endothelial cell agonists (26,27). We selectively desensitized endothelial cells to either LPS or endotoxic proteins by a 24-h pre-exposure to Salmonella LPS or a synthetic lipid-modified endotoxic peptide Pam 3 CSK 4 .…”

Section: Lps From S Minnesota Is Resistant To Polymyxin B Sequestratmentioning

confidence: 99%

Endotoxin Contamination of Ovalbumin Suppresses Murine Immunologic Responses and Development of Airway Hyper-reactivity

Watanabe

Miyazaki

Zimmerman

et al. 2003

Journal of Biological Chemistry

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106

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The reversible airway hyper-reactivity (AHR) of asthma is modeled by sensitizing and challenging mice with aerosolized ovalbumin. However, the C57BL/6 murine strain does not display the large increase in circulating IgG and IgE antibodies found in human atopy and asthma. We found that commercial ovalbumin was contaminated with lipopolysaccharide (LPS) in amounts sufficient to fully activate endothelial cells in an in vitro assay of the first step of inflammation. Desensitization of TLR4 by LPS pretreatment suppressed the inflammatory effect of ovalbumin. The presence of LPS was occult, because it does not require serum presentation and, like the LPS of Salmonella minnesota, was not suppressed by polymyxin B. Purified ovalbumin did not activate endothelial cells in vitro; however, endotoxinfree ovalbumin was far more effective than commercial material in stimulating IgE production and respiratory dysfunction in a C57BL/6 murine model of AHR. Moreover, endotoxin-free ovalbumin induced lung inflammation with alveolar enlargement and destruction in a histologic pattern that differed from the changes caused by commercial, endotoxin-contaminated ovalbumin. Reconstitution of purified ovalbumin with S. minnesota LPS decreased lung inflammation, decreased changes in lung function, and suppressed anti-ovalbumin antibody production. We conclude endotoxin contaminates ovalbumin preparations and that endotoxin co-administration with the ovalbumin antigen creates a state of tolerance in a murine model of AHR. Co-exposure to endotoxin and antigen occurs in humans through organic dusts, so murine models of AHR may reflect the clinical situation, but models based on commercial ovalbumin do not accurately reflect the effect of protein antigen alone on animal physiology.

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Section: Lps From S Minnesota Is Resistant To Polymyxin B Sequestratmentioning

confidence: 99%

Endotoxin Contamination of Ovalbumin Suppresses Murine Immunologic Responses and Development of Airway Hyper-reactivity

Watanabe

Miyazaki

Zimmerman

et al. 2003

Journal of Biological Chemistry

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106

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“…Similarly, both Lpp and LPS activate the complement cascade, coagulation cascade, and other inflammatory mediators (24)(25)(26)(27). In addition, Lpp purified from Y. enterocolitica synergizes with its LPS to induce production of proinflammatory cytokines in vitro and in vivo, leading to septic shock (28).…”

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confidence: 99%

“…In addition, Lpp purified from Y. enterocolitica synergizes with its LPS to induce production of proinflammatory cytokines in vitro and in vivo, leading to septic shock (28). Lpp binds to TLR-2 to activate host cells (27,29), while LPS interacts with a host cell receptor complex consisting of TLR-4 and its coreceptor, myeloid differentiation protein 2 (MD-2), to induce cellular responses (30)(31)(32)(33)(34)(35).…”

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confidence: 99%

Deletion of the Braun Lipoprotein-Encoding Gene and Altering the Function of Lipopolysaccharide Attenuate the Plague Bacterium

et al. 2013

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e Braun (murein) lipoprotein (Lpp) and lipopolysaccharide (LPS) are major components of the outer membranes of Enterobacteriaceae family members that are capable of triggering inflammatory immune responses by activating Toll-like receptors 2 and 4, respectively. Expanding on earlier studies that demonstrated a role played by Lpp in Yersinia pestis virulence in mouse models of bubonic and pneumonic plague, we characterized an msbB in-frame deletion mutant incapable of producing an acyltransferase that is responsible for the addition of lauric acid to the lipid A moiety of LPS, as well as a ⌬lpp ⌬msbB double mutant of the highly virulent Y. pestis CO92 strain. Although the ⌬msbB single mutant was minimally attenuated, the ⌬lpp single mutant and the ⌬lpp ⌬msbB double mutant were significantly more attenuated than the isogenic wild-type (WT) bacterium in bubonic and pneumonic animal models (mouse and rat) of plague. These data correlated with greatly reduced survivability of the aforementioned mutants in murine macrophages. Furthermore, the ⌬lpp ⌬msbB double mutant was grossly compromised in its ability to disseminate to distal organs in mice and in evoking cytokines/chemokines in infected animal tissues. Importantly, mice that survived challenge with the ⌬lpp ⌬msbB double mutant, but not the ⌬lpp or ⌬msbB single mutant, in a pneumonic plague model were significantly protected against a subsequent lethal WT CO92 rechallenge. These data were substantiated by the fact that the ⌬lpp ⌬msbB double mutant maintained an immunogenicity comparable to that of the WT strain and induced long-lasting T-cell responses against heat-killed WT CO92 antigens. Taken together, the data indicate that deletion of the msbB gene augmented the attenuation of the ⌬lpp mutant by crippling the spread of the double mutant to the peripheral organs of animals and by inducing cytokine/chemokine responses. Thus, the ⌬lpp ⌬msbB double mutant could provide a new live-attenuated background vaccine candidate strain, and this should be explored in the future.

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“…One obvious difference among various hosts is within the amino acid sequences of the complement proteins. For example, FH consists of 20 short consensus repeat (SCR) domains (28), and Ail is predicted to bind FH near SCR7 (12)(13)(14). Mouse SCR6-8 has 55% identity and 70% homology with human SCR6-8 (29), indicating that differences in this region of FH may influence interactions with Ail.…”

Section: Discussionmentioning

confidence: 99%

“…Both Lpp and LPS trigger toxic and biological responses in the hosts through the interaction of their lipid domains with Toll-like receptor 2 (TLR-2) and TLR-4, respectively, and by evoking the production of inflammatory cytokines such as tumor necrosis factor (TNF-␣), interleukin 6 (IL-6), and inter-feron gamma (IFN-␥) (14,15). Also, the complement and coagulation cascades are activated by both Lpp and LPS, and the production of other damaging inflammatory mediators contributes to the severity of infection (14,(16)(17)(18).…”

mentioning

confidence: 99%

Combinational Deletion of Three Membrane Protein-Encoding Genes Highly Attenuates Yersinia pestis while Retaining Immunogenicity in a Mouse Model of Pneumonic Plague

et al. 2015

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f Previously, we showed that deletion of genes encoding Braun lipoprotein (Lpp) and MsbB attenuated Yersinia pestis CO92 in mouse and rat models of bubonic and pneumonic plague. While Lpp activates Toll-like receptor 2, the MsbB acyltransferase modifies lipopolysaccharide. Here, we deleted the ail gene (encoding the attachment-invasion locus) from wild-type (WT) strain CO92 or its lpp single and ⌬lpp ⌬msbB double mutants. While the ⌬ail single mutant was minimally attenuated compared to the WT bacterium in a mouse model of pneumonic plague, the ⌬lpp ⌬ail double mutant and the ⌬lpp ⌬msbB ⌬ail triple mutant were increasingly attenuated, with the latter being unable to kill mice at a 50% lethal dose (LD 50 ) equivalent to 6,800 LD 50 s of WT CO92. The mutant-infected animals developed balanced T H 1-and T H 2-based immune responses based on antibody isotyping. The triple mutant was cleared from mouse organs rapidly, with concurrent decreases in the production of various cytokines and histopathological lesions. When surviving animals infected with increasing doses of the triple mutant were subsequently challenged on day 24 with the bioluminescent WT CO92 strain (20 to 28 LD 50 s), 40 to 70% of the mice survived, with efficient clearing of the invading pathogen, as visualized in real time by in vivo imaging. The rapid clearance of the triple mutant, compared to that of WT CO92, from animals was related to the decreased adherence and invasion of human-derived HeLa and A549 alveolar epithelial cells and to its inability to survive intracellularly in these cells as well as in MH-S murine alveolar and primary human macrophages. An early burst of cytokine production in macrophages elicited by the triple mutant compared to WT CO92 and the mutant's sensitivity to the bactericidal effect of human serum would further augment bacterial clearance. Together, deletion of the ail gene from the ⌬lpp ⌬msbB double mutant severely attenuated Y. pestis CO92 to evoke pneumonic plague in a mouse model while retaining the required immunogenicity needed for subsequent protection against infection. P athogenic yersiniae lead to two types of diseases: yersiniosis (typified by gastroenteritis caused by Yersinia enterocolitica and Y. pseudotuberculosis) (1) and plague (evoked by Y. pestis) (2, 3). Y. pestis has evolved from Y. pseudotuberculosis within the last 20,000 years by acquiring additional plasmids and pathogenicity islands as well as by deactivating some genes (4-6). This evolutionary adaptation allowed the plague bacterium to maintain a dual life-style in fleas and rodents/mammals and conferred the ability to survive in the blood instead of the intestine (3). Plague manifests itself in three forms: bubonic (acquired from an infected rodent through a flea bite), pneumonic (acquired either directly by aerosol transmission from an infected host's lungs through respiratory droplets or secondarily from bubonic plague), and septicemic (severe bacteremia either directly due to a flea bite or subsequent to bubonic or pneumonic plague) (2). T...

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Escherichia coliBraun Lipoprotein Induces a Lipopolysaccharide-Like Endotoxic Response from Primary Human Endothelial Cells

Cited by 42 publications

References 59 publications

Endotoxin Contamination of Ovalbumin Suppresses Murine Immunologic Responses and Development of Airway Hyper-reactivity

Endotoxin Contamination of Ovalbumin Suppresses Murine Immunologic Responses and Development of Airway Hyper-reactivity

Deletion of the Braun Lipoprotein-Encoding Gene and Altering the Function of Lipopolysaccharide Attenuate the Plague Bacterium

Combinational Deletion of Three Membrane Protein-Encoding Genes Highly Attenuates Yersinia pestis while Retaining Immunogenicity in a Mouse Model of Pneumonic Plague

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